Ten percent or more of mothers with chronic Trypanosoma cruzi infection give birth to infected infants, many of whom will develop life-threatening sequelae of Chagas disease at birth, shortly after birth or later in life. Until recently, congenital Chagas disease has been neglected as a public health problem. Now that regional Chagas disease control programs have begun to dramatically reduce the incidence of vector-borne and transfusion-associated transmission, maternal-to-infant transmission is the most frequent route in many endemic areas. There are 10-12 million persons living with chronic T. cruzi infection in Latin America; hundreds of thousands of Latin American immigrants to the United States and other industrialized countries are infected as well. Perhaps a third of these are women and girls under the age of 45 years who can transmit the parasite to their offspring during sequential pregnancies because infection is lifelong. Recent studies have demonstrated that treatment of congenitally infected infants with antitrypanosomal drugs shortly after birth is highly effective. However, cure is increasingly difficult to achieve as the child grows older. The Pan American Health Organization recommends diagnosis and treatment of all infants with congenital Chagas disease, but technical, logistical, and economical obstacles have prevented any country from implementing a nationwide congenital Chagas disease intervention program. In the majority of infected infants, congenital Chagas disease is subclinical or presents with subtle nonspecific findings. Therefore, the most promising approach to congenital Chagas disease is universal laboratory-based screening of infants for T. cruzi infection. At present, there is no sufficiently sensitive and logistically feasible diagnostic test for congenital Chagas disease in the first days of life. The goal of this application is develop a sensitive and specific diagnostic assay for congenital Chagas disease that could be used for mass screening of newborns. We will also study the epidemiology of congenital Chagas disease in Santa Cruz, Bolivia and identify maternal and infant risk factors for congenital transmission of T. cruzi, in order to develop strategies for efficient targeting and implementation of screening programs, and to provide the basis for developing other novel approaches to decrease the prevalence and adverse sequelae. [unreadable] [unreadable] [unreadable]